To evaluate the effects of topical naltrexone on wound healing in freshwater fish. 25 blackbelt cichlids (Vieja maculicauda). A randomized, controlled, experimental trial was performed, with each individual serving as its own control. Bilateral 6-mm periepaxial cutaneous wounds were created in the body-wall skin of each fish under anesthesia. Three treatment groups were as follows: topical 0.04% naltrexone in administration vehicle (iLEX ointment; iLEX Health Products) at day 0 only (n = 10), topical 0.04% naltrexone in iLEX every 72 to 96 hours (n = 10), or iLEX only every 72 to 96 hours (n = 5) for 10 total treatments. The contralateral wound was left untreated as a control. Fish were maintained in a common enclosure at 24.7 to 25.4 °C for 35 days. Macroscopic wound assessment and image collection were performed every 72 to 96 hours. On day 35, fish were humanely euthanized, and skin samples were collected for histopathology. Time to complete visual resolution of wound healing was faster (P = .002) in wounds treated every 72 to 96 hours with topical 0.04% naltrexone in iLEX (day 19.4) compared to untreated wounds (day 23.3). An interaction between treatment and day was observed (P = .002), with fish treated with 0.04% naltrexone in iLEX every 72 to 96 hours having reduced (P < .05) wound area compared to both controls and fish treated with topical 0.04% naltrexone in iLEX once. No significant differences were noted in histologic sections of wound sites examined at day 35. Fish improved earlier postsurgery and time to complete wound resolution was faster in wounds treated with topical 0.04% naltrexone in iLEX every 72 to 96 hours.